Medicinal Agent

ABSTRACT

Medicine and pharmacology, in particular a medicinal agent exhibiting anti-tumoral and immunomodulatory actions and including a tri-p-amino-thiphenyl-chlormethan tetramethylated, pentamethylated or hexamethylated derivative, the mixtures thereof or the combination thereof with dextrin. The agent of this invention exhibits a high activity and a reduced side effect.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to the medical sector, more especially withanti-blastomatous medicines, and also with preparations that influencethe immune system.

2. Discussion of Related Art

The preparation adriamycin is known and is an antibiotic of theanthracyline group with a marked anti-blastomatous effect (see M. D.Maschkowskij, Medicinal Agents, Medicine Publishers, Moscow, 1985,Volume 2, Pages 460-461).

The preparation is used in the form of a hydrochloride solution,exclusively intravenously as it causes subcutaneous tissue necrosis.Also, the preparation has a cardiotoxic effect and can cause cardiacpain, cardiac insufficiency and a lowering of the blood pressure.

The nearest prototype is cyclophosphan which is produced as a whitecrystalline powder that is water-soluble (1:50), lightly alcoholic anddifficult to dissolve in an isotonic sodium chloride solution (forexample, M. D. Maschowskij, Medicinal Agents, Medicine Publishers,Moscow, 1985, Volume 2, Pages 433-434.)

The known preparation has a wide, anti-blastomatous spectrum of activityand at the same time is an immunosuppressant, when such is used however,side effects can be observed, such as, for example, dizziness, nauseaand vomiting, and often hair loss.

SUMMARY OF THE INVENTION

It is one object of this invention to provide a medicine that is similarto the prototype but that has a wide spectrum of activity without sideeffects.

Methyl violet, which belongs to the group of triaminotriphenylmethanedyes, is known and provides salts with colored organic cations (see, forexample, Abbreviated Chemical Encyclopaedia, Russian EncyclopaediaPublishers, Moscow, 1967, Volume 5, Pages 252-253) and provides amixture of nitrogen methylised tri-p-aminotriphenylchloromethane thatincludes tetra methyl, penta methyl and hexamethyl derivatives. (See forexample, StainsFile methyl violet 2B, 6B and 10B.)(http://members.pgonline.com/bryand/StainsFile/dyes/42535.htm).

The structural formula of tri-p-aminotriphenylchloromethane has thefollowing form:

in which, for example, R₁═N(CH₃)₂, R₂═H, R₃═H, R₄═N(CH₃)₂, R₅═H,R₆=either NH₂ or NHCH₃ or N(CH₃)₂.

Methyl violet 2B (tetramethyl pararosanilin chloride), in this case, isa tetramethyl derivative of tri-p-aminotriphenylchloromethane (in thestructural formula R₆═NH₂, designations for R₁, R₂, R₃, R₄ and R₅correspond to the abovementioned, total formula C₂₃H₂₆N₃CI, molecularweight 379.94) and is a water-soluble and alcohol-soluble, fine-grained,brown, crystalline powder with a hint of green. Methyl violet 6B(pentamethyl pararosanilin chloride) is a pentamethyl derivative oftri-p-aminotriphenylchloromethane (in the structural formula R₅═NHCH₃,designations for R₁, R₂, R₃, R₄ and R₅ correspond to the abovementioned,total formula C₂₄H₂₈N₃CI, molecular weight 393.97) and is a homogeneous,water-soluble and alcohol-soluble, fine-grained, crystalline powder in abronze-green color, also known as basic violet K or respectively methylviolet. Methyl violet 10B (hexamethyl pararosanilin chloride) is ahexamethyl derivative of tri-p-aminotriphenylchloromethane (in thestructural formula R₆═N(CH₃)₂, designations for R₁, R₂, R₃, R₄ and R₅correspond to the above-mentioned, total formula C₂₅H₃₀N₃CI, molecularweight 407.99) and is a water-soluble and alcohol-soluble, green,crystalline powder, also known as crystal violet or respectively basicviolet 3 (see, for example, Catalogue of Harmful Substances in Industry,Part 1, Organic Substances, Chemical Literal Publishers, Edition 4,Leningrad, 1963, Pages 638-639, StainsFile Methyl Violet 2B, 6B and10B.) (http://members.pgonline.com/bryand/StainsFile/dyes/42535.htm) andReference Work for Chemists, Chemistry Publishers, Leningrad, 1967,Volume 6, Page 759). The above-mentioned derivatives are designated insome sources as gentian violet (see, for example, StainsFile MethylViolet 2B, 6B and 10B)(http://members.pgonline.com/bryand/StainsFile/dyes/42535.htm).

Known is a dye mixture, including comprising methyl violet and fuchsineunder the designation dahlia violet, a water-soluble, alcohol-soluble,green, crystalline powder, and comprising methyl violet and dextrinunder the designation gentian violet, which is a water-soluble, brightgreen powder (see, for example, Catalogue of Harmful Substances inIndustry, Part 1, Organic Substances, Chemical Literature Publishers,Edition 4, Leningrad, 1963, Page 639).

These dyes are mainly used in the industry, for example to color tissue.The use of crystal violet (hexamethyl derivative oftri-p-aminotriphenylchloromethane), however, in gynaecology andpaediatrics is known to treat candidid (see http://www.oncology.com).

A dextrin, which is a polysaccharide mixture, is known and used intissue coloring (see N. L. Glinka, General Chemistry, ChemistryPublishers, 1978, Page 494).

The above object is achieved through the intermediary of animmuno-modulating, anti-blastomatous medicine, in which the medicineincludes derivatives of tri-p-aminotriphenylchloromethane that can berepresented pharmacologically, and the medicine has the followingstructural formula:

wherein, for example, the following applies: R₁═N(CH₃)₂, R₂═H, R₃═H,R₄═N(CH₃)₂, R₅═H, a R₆=either NH₂ or NHCH₃ or N(CH₃)₂.

The medicine, in this case, includes thetri-p-aminotriphenylchloromethane in the form of either its tetramethylderivative, in the structural formula R₆═NH₂, or its pentamethylderivative, in the structural formula R₆═NHCH₃, or its hexamethylderivative, in the structural formula R₆═N(CH₃)₂, wherein thedesignations of the named derivatives R₁, R₂, R₃, R₄ and R₅ correspondto the above-mentioned.

Also, the medicine includes the tri-p-aminotriphenylchloromethane eitheras a mixture of its tetramethyl and pentamethyl derivatives in the ratioof 2.0-98.0 percent by volume tetramethyl derivative and the remainderpentamethyl derivative or as a mixture of its tetramethyl and hexamethylderivatives in the ratio of 2.0-98.0 percent by volume tetramethylderivative and the remainder hexamethyl derivative or as a mixture ofits pentamethyl and hexamethyl derivatives in the ratio of 2.0-98.0percent by volume pentamethyl derivative and the remainder hexamethylderivative or as a mixture of its tetramethyl, pentamethyl andhexamethyl derivatives in the ratio of 1.5-97.0 percent by volumetetramethyl derivative, 1.5-97.0 percent by volume pentamethylderivative and the remainder hexamethyl derivative.

DETAILED DESCRIPTION OF THE INVENTION

The above object is achieved through the intermediary of animmuno-modulating, anti-blastomatous medicine wherein the medicinecomprises a mixture of dextrin and pharmacologically representablederivatives of the tri-p-aminotriphenylchloromethane, for example, inthe form of either tetramethyl or pentamethyl or hexamethyl derivativesor respectively a mixture of tetramethyl and pentamethyl derivatives ora mixture of tetramethyl and hexamethyl derivatives or a mixture ofpentamethyl and hexamethyl derivatives or respectively a mixture oftetramethyl, pentamethyl and hexamethyl derivatives in the ratio of10.0-95.5 percent by volume of the corresponding derivative orrespectively derivative mixture of the tri-p-aminotriphenylchloromethaneand the rest dextrin.

In this case, the mixture of tetramethyl and pentamethyl derivatives ofthe tri-p-aminotriphenylchloromethane is selected at a ratio of 2.0-98.0percent by volume tetramethyl derivative and the rest pentamethylderivative. The mixture of tetramethyl and hexamethyl derivatives isselected at a ratio of 2.0-98.0 percent by volume tetramethyl derivativeand the rest hexamethyl derivative. The mixture of pentamethyl andhexamethyl derivatives is selected at a ratio of 2.0-98.0 percent byvolume pentamethyl derivative and the rest hexamethyl derivative. Themixture of tetramethyl, pentamethyl and hexamethyl derivative isselected at a ratio of 1.5-97.0 percent by volume tetramethylderivative, 1.5-97.0 percent by volume pentamethyl derivative and therest hexamethyl derivative.

The medicine with an immuno-modulating and anti-blastomatous effectcontains a pharmacologically representable tetramethyl or pentamethyl orrespectively hexamethyl derivative of thetri-p-aminotriphenylchloromethane or of its mixtures, or respectivelymixture produced from one derivative and dextrin or mixtures producedfrom the derivatives and dextrin.

The tetramethyl derivative of the tri-p-aminotriphenylchloromethane, inthis case, is methyl violet 2B (tetramethyl pararosanilin chloride, inthe structural formula R₆═NH₂, the designations for R₁, R₂, R₃, R₄ andR₅ correspond with the abovementioned, the total formula is C₂₃H₂₆N₃CI,molecular weight is 379.94), which is a water-soluble andalcohol-soluble, fine-grained, brown, crystalline powder with a hint ofgreen. The pentamethyl derivative is methyl violet 6B (pentamethylpararosanilin chloride, in the structural formula R₆═NHCH₃, thedesignations for R₁, R₂, R₃, R₄ and R₅ correspond to theabove-mentioned, the total formula is C₂₄H₂₈N₃CI, the molecular weightis 393.97), which is a homogeneous, water-soluble and alcohol-soluble,fine-grained, crystalline powder that is bronze-green in color. Thehexamethyl derivative is methyl violet 10B (hexamethyl pararosanilinchloride, in the structural formula R₆═N(CH₃)₂, the designations for R₁,R₂, R₃, R₄ and R₅ correspond to the abovementioned, the total formula isC₂₅H₃₀N₃CI, the molecular weight is 407.99), which is a water-solubleand alcohol-soluble, green, crystalline powder.

Mixtures from derivatives of the tri-p-aminotriphenylchloromethane andmixtures of its derivatives and dextrin in the above-mentioned ratiosprovide a water-soluble, greenish powder.

Derivatives of the tri-p-aminotriphenylchloromethane in the form of itsmixtures are obtained by subsequent separation as tetramethyl,pentamethyl and hexamethyl derivatives by methylizing parafuchsin withiodomethyl (see A. N. Nesmejanow, N. A. Nesmejanow, Basics of OrganicChemistry, Chemistry Publishers, Moscow, 1974, Volume 2, Page 200),wherein the pentamethyl derivative (basic violet K) can also be obtainedby oxidizing dimethylaniline with copper salts (see Harmful Substancesin Industry, Part 1, Organic Substances, Chemical Literature Publishers,Edition 4, Leningrad, 1963, Page 639) and pure hexamethyl derivative(crystal violet) can be obtained by condensation ofdi-(p-dimethylamino)-benzophenone (Michler's ketone) withdimethylaniline and subsequent acidifying (see A. N. Nesmejanow, N. A.Nesmejanow, Basics of Organic Chemistry, Chemistry Publishers, Moscow,1974, Volume 2, Page 200).

The target product in the form of a medicine that is ready for use isobtained by purifying the mixtures obtained, for example byre-crystallization as well as by using chromatography by passing watersolutions of these salts through an adsorption layer, for examplechromatographic protoplasm or bentonite clay in the separation column.

Dextrin is obtained by heating dry starch to 200-250° C. (see N. L.Ginka, General Chemistry, Chemistry Publishers, 1978, Page 494).

The required mixtures are obtained by selecting specific substances at apredetermined ratio.

The medicine containing pharmacologically representable derivatives oftri-p-aminotriphenylchloromethane as well as the mixtures of dextrin andthe derivatives have an anti-blastomatous effect, which, is accompanied,for example, by the therapeutic effect that has been established by theinventor, the effect being designated as disymmetrical and beingmeasured at different temperatures at different parts of the body. Thiseffect can be seen, for example, in a temperature range of 2-3° C. 0.5-2hours after the medicine has been taken and lasts for 3-4 hours (see M.W. Kutuschow, Cancer, Healing is Possible, Newa Publishers,St-Petersburg, 2003). The medicine also has an anabolic activity andpromotes cell and humeral protection factors of the body.

The method of activity of the pharmacologically representablederivations of the medicine containing tri-p-aminotriphenylchloromethaneis based on ionizability, through which interaction with phospholipidsof the cell membranes occurs to disturb the balance of the ionictrans-membrane potential, cell death thereby resulting. Theinvestigations carried out by the inventor also showed that thatmedicine is an inhibitor of the mitochondrial ferments of maliciouscells and causes the mitochondria of the carcinoma cells to die,suppressing the NADPH cytochrome c reductase activity, thereby blockingenergy (see Shumyantseva V. V., Uvarov V. Yu., Byakova O. E., ArchakovA. I., Biochem. Molec. Biol. Intern, 1996, No. 38, Pages 829-838). It isestablished that the effectiveness of the medicine is all the greater,the more its adsorption spectrum is pushed in the direction of the UVrange. In addition, it is established that dextrin as one of thesubstances considerably reduces the toxicity of the medicine andconsequently expands the dosing range.

This has been confirmed through laboratory tests and patient tests, theblood being tested for the immunological values of the white blood celland lymph systems.

Produced as technically or chemically pure salt or respectively highlypurified or medically purified or medically highly purified salt, inaccordance with pharmacopeia requirements on medicines (see Law of theRussian Federation on Medicines No. 86-FZ dated Jun. 22, 1998 and thebranch standard OST 91500.05.001,00, Quality Standards for Medicines,Conditions, publication in the Rossijskaja Gaseta dated Nov. 28, 2001),the medicine can be given to the patient, with reference to the degreeof purification of the preparation, in an isotonic sodium chloridesolution intravenously and perorally in capsules as well as in the formof a substance in ointments or as medical enemas or respectivelysuppositories, the use of the medicine not causing any allergic or otherside effects and its effectiveness (in the treatment of certainillnesses) in some cases being greater than that of the prototype.

The results of tests on the working mechanism of the medicinal agent inaccordance with this invention are detailed in the examples 1-3 below,and the possible use of the medicinal agent is confirmed by the examples4-10 below.

EXAMPLE 1

In test glasses (14×10 ml test glasses) of the first group with humanmalignant melanoma A 375 in buffer solution, the medicinal agent wasintroduced in a dilution of 10⁻⁷ mmol/l in the form of methyl violet 2B(tetramethyl derivative of the tri-p-aminotriphenylchloromethane),methyl violet 6B (pentamethyl derivative of thetri-p-aminotriphenylchloromethane), methyl violet 10B (hexamethylderivative of the tri-p-aminotriphenylchloromethane), mixtures of methylviolet 2B and methyl violet 6B, methyl violet 2B and methyl violet 10B,methyl violet 6B and methyl violet 10B, mixtures of methyl violet 2B,methyl violet 6B and methyl violet 10B (the substances at identicalratios), mixtures of dextrin and its salts as well as mixtures ofdextrin and the specified mixtures of these salts (at a ratio of 50percent by volume dextrin and the rest salt or the rest salt mixture (atthe specified ratio)). The same was carried out with a dilution of10⁻⁹mol/l (14×10 ml test glasses).

In test glasses of the second group with HFF (human forskin fibroblast),the medicine was introduced in the same compositions and dilutions.

In addition, a third control group of test glasses (6 glasses) wasformed with the same cancer cell pool and fibroblasts, into whichadriamycin and cyclophosphan in the same dilution was introduced, aswell as a corresponding test glass group with a physiological saltsolution.

After thermostatization of the above-mentioned test glasses for a weekat 37° C. (in the dark), the contents were analyzed.

The results obtained were as follows.

In the test group with the medicine in a dilution of 10⁻⁷ mmol/l, themedicine suppresses the replication of the melanoma cells by 86-93% incomparison to the replication of these cells in the test glass with aphysiological salt solution and suppresses the replication of thefibroblasts by 25-27%, the phenotype being approximately identical forall compositions of the medicine.

In test glasses of the control group with adriamycin, a replication ofthe melanoma cells was reduced by 42% and with cyclophosphan it wasreduced by 55%.

In the test group with the medicine in a dilution of 10⁻⁹ mmol/l, themedicine suppresses the replication of the melanoma cells by 75-90% incomparison to the replication of these cells in a physiological saltsolution and suppresses the replication of the fibroblasts by 5-10%, thereplication of the melanoma cells being reduced by 30% in test glassesof the control group with adriamycin and by 35% in test glasses withcyclophosphan.

The data obtained points to the fact that the medicine put forward, evenin very strong dilutions, has a marked anti-blastomatous effect andgreater activity than known anti-blastomatous preparations and ischaracterized by a small cytotoxic effect against fibroblasts.

EXAMPLE 2

In test glasses (50×10 ml test glass) of the test group with “smooth”microsomes of cancer cells MCF-7 (mammary gland adeno carcinoma) in abuffer solution, the medicinal agent was introduced in a dilution of10⁻⁵ mmol/l in the form of mixtures of methyl violet 2B (tetramethylderivative of the tri-p-aminotriphenylchloromethane) and methyl violet6B (pentamethyl derivative of the tri-p-aminotriphenylchloromethane) intwo ratios: 98.0 percent by volume methyl violet and the rest methylviolet 6B and 98.0 percent by volume methyl violet 6B and the restmethyl violet 2B, methyl violet 2B and methyl violet 10B (hexamethylderivative of the tri-p-aminotriphenylchloromethane) in 2 ratios: 98percent by volume methyl violet 2B and the rest methyl violet 10B, ofmethyl violet 6B and methyl violet 10B in two ratios: 98.0 percent byvolume methyl violet 6B and the rest methyl violet 10B and 98.0 methylviolet 10B and the rest methyl violet 6B, mixtures of methyl violet 2B,methyl violet 6b and methyl violet 10B in four ratios: 1) 2.0 percent byvolume methyl violet 2B, 50.0 percent by volume methyl violet 6B and therest methyl violet 10B, 2) 50.0 percent by volume methyl violet 2B, 2.0percent by volume methyl violet 6B and the rest methyl violet 10B, 3)50.00 percent by volume methyl violet 6B, 2.0 percent by volume methylviolet 10B and the rest methyl violet 2B, 4) 20.0 percent by volumemethyl violet 2B, 25.0 percent by volume methyl violet 6B and the restmethyl violet 10B and mixtures of dextrin and salts and the specifiedmixtures of these salts (in the abovementioned compositions) at theratio: 10.0, 25.0, 75.0, 90.0 percent by volume dextrin and the restsalt or respectively salt mixture. The same was also implemented with adilution of 10⁻⁹ mmol/l.

In test glasses (10 ml) of the second group with microsomes of ratliver, the medicine was introduced in the same compositions anddilutions.

In addition, a third (control) group of test glasses (6) was formed withmicrosomes of the same cancer cell pool and rat liver, into whichadriamycin and cyclophosphan were introduced in the same dilution, and acorresponding test glass group with physiological salt solution.

In the test glasses of the groups the concentration of cytochrome C wasdetermined, which is 50 μM for cancer microsomes and 20 μM formicrosomes of rat liver.

After the thermostatization of the above-mentioned test glasses over 20min at 25° C. (in the dark), the contents were analyzed.

The results obtained were as follows.

In the test group, the concentration of cytochrome C in the test glasseswith the introduced salt mixture was determined in the range up to 60 μMand in the test glasses with the introduced mixtures of salt and dextrinit was in the range of up to 65 μM.

In the test glasses with adriamycin and cyclophosphan, the concentrationof cytochrome C was 40-45 μM. In the test glass with the physiologicalsalt solution no changes in the concentration of cytochrome C wereobserved. Liver microsomes of rats were not influenced by thepreparation. The concentration of cytochrome C in all test glassesremained in the region of 19-20 μM.

The results obtained lead to the assumption that the medicine promotesthe releasing of the “aggressive” protein of cytochrome C from themembranes of the cancer cell mitochondria, which causes an apoptosis ofthese cells, triggering a destruction mechanism of the DNS throughcaspases (see Wilson B. E., Mochon E. A., Boxer L. M., Induction ofblc-2 expression by phosphorylated CREB proteins during B-cellactivation and rescue from apoptosis, Mol. Cell. Biol., 1996, V. 16,Pages 5546-5556).

EXAMPLE 3

A reaction to the medicinal agent in the form of salts of methyl violet2B, methyl violet 6B and methyl violet 10B as well as mixtures of thesesalts with dextrin was tested in B-57 type mice in two ratios: 5.0percent by volume dextrin and the rest salt as well as 95.0 percent byvolume dextrin and the rest salt.

The test group included 60 mice and was divided into 6 sub groups eachof 10 mice. The control group included 10 mice; the sub groups of thetest group, in this case, were kept separate from the control group, andmice in each sub group were identified from 1 to 10 with a dye, in thiscase with Viride Nitens.

The test group received the medicinal agent over 10 days: the first subgroup received the mixture produced from 2.0 percent by volume dextrinand the rest methyl violet 2B, the second sub group received the mixturefrom 90.0 percent by volume dextrin and the rest methyl violet 2B, thethird sub group the mixture from 5.0 percent by volume dextrin and therest methyl violet 6B, the fourth sub group received the mixture from90.0 percent by volume dextrin and the rest methyl violet 6B, the fifthsub group received the mixture from 5.0 percent by volume dextrin andthe rest methyl violet 10B and the sixth sub group received the mixturefrom 90.0 percent by volume dextrin and the rest methyl violet 10B. Ineach sub group, mice Nos. 1 to 8 received the preparation as a drink (ina water solution) and mice Nos. 9-10 received it as an injection intothe belly fur. The single dose for mice Nos. 1-2 was 2 mg, for Nos. 3-45 mg, for Nos. 5-6 10 mg, for Nos. 7-8 20 mg and Nos. 9-10 15 mg per 1ml injection solution. The mice in the control group did not receive anypreparation.

Results: one week after the introduction of the medicinal agent nodifferences in the behavior of the even sub groups and the controlgroup. Animals Nos. 5-6 in the uneven sub groups could hardly move,animals Nos. 7-8 in the uneven sub groups died.

The mice with uneven numbers in all the sub groups were killed on the10^(th) day and mice with even numbers were killed on the 21^(st) day.

Traces of the medicinal agent were established in the kidneys of theanimals Nos. 3-6 in the uneven sub groups and of the animals Nos. 5-8 inthe even groups.

A histological test established a minimum influence of the mixture withmethyl violet 10B (identified as B.V.2) and a maximum influence of themixture with methyl violet 2B.

It can be concluded, taking the ratios of mass into account, that thesingle dose of 2.0 g is representable for the human body. More accuratedata, however, can only be supplied after corresponding tests.

EXAMPLE 4

B57 type mice in the test and control group (60 mice each) were injectedwith melanoma 16. The test group were divided into 6 sub groups and thecontrol group was divided into 3 sub groups, each with 10 mice. Each subgroup in the test group received 5 mg medicinal agent in the form of awater solution of methyl violet 2B, methyl violet 6B and methyl violet10B as well as mixtures of these salts with dextrin at a ratio of 25:75percent by volume.

The first and second sub group in the control group received a dose of 5mg in a water solution of adriamycin and cyclophosphan in the form of adrink; the third sub group did not receive any preparation.

Results: On the 39^(th) day of the test, 39 of the 60 mice in the testgroup remained alive. 11 mice (4 from the first sub group and 3 fromeach of the second and third sub groups and one mouse from the fourthsub group) died on the 19^(th) day. 5 mice (2 from each of the first andsecond sub groups and one from the third sub group) died on the 23^(rd)day and 5 mice (2 from the first and one each from the second, fourthand fifth sub groups) died on the 34^(th) day of the test. Seventeensurviving mice (one from the first, three from the second, one from thethird, 4 each from the fourth and fifth and 3 from the sixth sub group)had blastomas of ca. 0.2×0.2 mm; no blastoma was established on visualexamination of the remaining mice. The surviving mice were killed on the36^(th) day of the test. In the dissection, 9 mice (one from the first,4 from the fourth and 2 each from the fifth and sixth sub groups) werefound to have isolated, pulmonary metastasis and 4 of the said 9 mice(one from the first, 2 from the second and one from the fifth sub group)also had hepatic metastasis. The other mice had no metastasis and novisible changes of the inner organs.

The first and second sub group of the control group: 2 mice in the firstsub group and 5 mice in the second sub groups survived as far as the36^(th) day of the test. The blastomas had average dimensions of 1.5×1.5cm. During the dissection, lung and liver injuries were established.

All the mice in the third sub group died on the 10^(th), 12^(th),20^(th) and 25^(th) day. On investigation, bleeding blastomas of theback with an average size of 2.5×2.0 cm were established. A histologicaltest established total lysis of the lung.

Conclusions: the medicinal agent has an anti-blastomatous effect anddoes not cause any side effects.

EXAMPLE 5

Non-Hodgkin's lymphoma (NHL) was diagnosed in a 3-year old dog weighing16 kg. The condition was serious, difficulty in breathing and cachexia.In the area of the neck there were growths to the size of 7×5 cm on theright and 11×10 on the left. Several growth-like images in themediastinum were visible on the X-ray that was taken on 20.10.99.

Treatment with the medicinal agent was started on 30.10.99. The dog wasgiven 500 mg methyl violet 2B per 500 ml physiological salt solutionintravenously in the form of drops. After three days a mixture of methylviolet 2B and methyl violet 6B (250 mg each) per 500 ml physiologicalsalt solution was given intravenously and a peroral dose of a mixture ofdextrin, methyl violet 2B, methyl violet 6B and methyl violet 10B (50 mgof each substance in a single dose of 200 mg) in the form of powdertwice a day. The mixture of methyl violet 2B and methyl violet 6B wasgiven repeatedly intravenously as well as a peroral dose of theabove-mentioned mixture with dextrin after one week.

Two weeks after the start of the treatment, an improvement was observedin the general condition and in the biochemical and clinical bloodparameters. After three weeks, the visible growths were 2.5×smaller.

The treatment with methyl violet 2B and methyl violet 6B comprised aweekly intravenous intromission of the mixture for 3 months; the peroraldose of the abovementioned mixture (with dextrin) was reduced daily.

In an examination after the treatment, the dog proved to be in goodcondition, its weight was 19.5 kg, and there were no growths on theneck. There was no pathology in the blood results. Isolated small lungmetastasis could be seen in the X-ray taken on 02.02.2000.

EXAMPLE 6

A sarcoma of the right forearm and pulmonary metastases were diagnosedon a dog aged 6 years, weighing 21 kg. The x-ray that was taken on10.07.2002 showed a breakdown of the periosteum and of the 1^(st) to7^(th) right-hand ribs, several pulmonary metastases on the right andleft and a growth of 10×15×12 cm.

On 12.07.02 treatment was started. Every other day a dose made up of 50mg methyl violet 10B (identified as B.V.2), diluted with 9% NaCl anddissolved in 250 ml water was administered intravenously in an amount of2 ml; paste bandages were wrapped around the growth daily (2% methylviolet 10B and the remainder baby lotion).

Three weeks after the start of the treatment, the dimensions of thegrowth had reduced to 7×7×3 cm. The condition was stable and after afurther two weeks it was satisfactory; the X-ray showed an encapsulatedgrowth of 2×2,5×1 cm and traces of rib and lung metastases.

EXAMPLE 7

Exstirpation of the uterus and the surrounding area on account of cancerof the right ovary was performed on patient I who was 35 years old andhad visited the doctor in November 2002. The tomogram that was dated28.08.02 showed a recidiv, a growth of 8.8×9.8×14 cm growing through theurinary bladder and the rectum.

The patient was treated with an enema of the rectum: over five days oncea day, after five procedures once every other day and thereafter everythird day for 15 enemas. She was treated with a single dose of 20 mgmedicinal agent (B.V.2) per 15-20 ml water, diluted in 2 ml 70% ethylalcohol.

After 2 weeks of the treatment, ultrasound showed the size of the growthto be 3.8×4.2×3.1 cm with smooth contours; the growth had receded fromthe wall of the rectum, and the deformation of the urinary bladder wallwas slight.

After the treatment, the growth according to an ultrasound test wasencapsulated and was 1.3×2.0×1.6 cm in size; the capsule walls were 0.5cm thick and there were no problems. Continuation of the treatment withintervals (1.0-1.5 months) was recommended. In a control investigationusing ultrasound on 02.03.04, the growth was no longer to be found.

The blood parameters before treatment were: leucocytes up to 10,000,erythrocytes 2.5 million and thrombocytes 110,000. The blood parametersafter the treatment were: leucocytes 9,000, erythrocytes 5.5 million andthrombocytes 300,000.

EXAMPLE 8

A papillary thyroid cancer was diagnosed in 62 year old patient R.Before the treatment, the growth according to an ultrasoundinvestigation was in the right lobe and was 5×3×1.7 cm in size.

The patient was treated with the medicinal agent (B.V.2) for 2 weeks;one gelatine capsule two times a day with 20 mg medicinal agentperorally after food and enemas in a single dose of 100 ml solution,comprising 50 mg medicinal agent powder, diluted in 2 ml 70% ethylalcohol and dissolved in 100 ml water solution with 0.9% NaCl.

Over 7 days, 3 hours after taking the dose of the medicinal agent thepatient was observed to be under a dissymmetric effect, which wasmanifested through sudden signs of fever and different temperatures onthe right and left sides of the body, from 35.4-36.9° C. on the rightand 37.3-38.6° C. on the left, over 1.0-1.5 hours. The above-mentionedtemperature differences disappeared almost completely when thepreparation was taken again.

After the treatment, an ultrasound investigation showed a primary growthand no metastases. In a control test after 2 months, the condition wassatisfactory, and there were no complications.

EXAMPLE 9

Patient Sch, aged 18, was diagnosed in September 2002 with a tumour of2×2, 5×2 cm in her right breast. The mammogram showed a fibrocysticmastopathy in the right breast. A biopsy sample showed atypical cells.

The breast was painted two or three times in the area of the growth witha mixture of B.V.2 powder and baby lotion at a ratio of 10:90%. Repeatedbiopsy samples after 1.5 months showed no atypical cells. The growthcould practically no longer be felt.

EXAMPLE 10

An adeno carcinoma of the lower colon with liver metastases wasdiagnosed on patient Ju, aged 48 years. In April 1999, a colon was cutout and a colostomy put in. Prophylactic chemotherapy was not effective(renewed pain in the stomach area, periodic vomiting, general weakness).In August 2002, the patient went back to his doctor on account of thesecomplications. A tomogram dated 21.09.02 showed a growth-like formationof 7.0×5.5 cm in the area of the spleen, uneven contours and metastasesin the right liver lobes.

The following treatment was carried out: 10 days of peroral doses of amixture of dextrin and methyl violet 2B, methyl violet 6B and methylviolet 10B (B.V.2) diluted with 100 ml water (at a corresponding ratioof 25:30:30:15) 1.0 g twice a day 30 minutes before food as well as inthe mornings and evenings 0.5 g B.V.2, dissolved in 50 ml water, intothe colostomy. Over and above this, with the agreement of the patient,an intravenous intromission of 500 ml of a 1% solution of thepreparation to increase the effect. The treatment lasted for 3 months.After the treatment, the condition was satisfactory. The tomogram showedno growths in the abdomen and no hepatic metastases. The bloodparameters were in order.

EXAMPLE 11

When patient N, 25 years old, went to the doctor on 23.10.1999, she wasdiagnosed with complications of alopecia totalis, periodic weakness anddepression.

Alopecia began with eye brow and eye lash hair loss 6 years ago afterthe flu, and then 6 months later with head hair loss. The illness wastreated for 2 years locally with hormones and ointments. At an anamnesisit was established that the patient had had acute respiratory disease atthe age of 7 and a week later had caught chickenpox, probably givingrise to a latent auto-immune disease. An auto-immune disease withcomplicated alopecia totalis was diagnosed. Blood tests for cellular andhumeral immunity confirmed the diagnosis.

Two treatments were carried out using the medicinal agent. The firsttreatment was a dose of a mixture of dextrin, methyl violet 2B, methylviolet 6B and methyl violet 10B at a ratio of 25:25:25:25 at a regime of0.2 ml 1% water solution twice a day 30 minutes before food over 3months.

After 3 weeks of the treatment, gnawing pain appeared in the kidneys.This was assumed to be a reaction of the adrenal glands to thesuppression of fixed, hyperactive microphages caused by the preparation.A tomogram of the abdomen, kidneys and adrenal glands showed that theleft and right adrenal glands were larger and deformed. The treatmentwas continued and after one week the pain in the kidneys disappeared.After 2 months of the treatment, healthy hair appeared on her head andon her legs.

After the first batch of treatment, the treatment was interrupted for 2months and then an additional batch of treatment of 2 months was carriedout, which consisted of one dose of methyl violet 10B (B.V.2) with anamount of 0.5 ml in a 1% water solution twice a day 30 minutes beforefood.

One year after the start of the treatment, the thickness and structureof the body hair is typical. At the moment no hair loss is observed. Thecontrol tomogram dated 12.03.03 showed that the adrenal glands were notenlarged and were in the form of a triangle. The blood parameters werein order.

The following table shows the test results with reference to thecellular and humeral immunity: Before treatment After 4 weeks After 6months Immunoglobulin A 60 170 249 Immunoglobulin M 50 98 190Immunoglobulin G 800 1400 1750 T-lymphocytes, % 34.0 65.0 74.0B-lymphocytes, % 10.0 14.0 16.0 Phagocytosis of 43.0 60.0 67.3 latexparticles, % TNF 15.6 23.0 32.5 Helper cells, % 26.0 30.0 38.0Suppressor cells, % 12.0 18.0 17.0 Killer cells, % 16.0 19.0 19.0

1. A medicinal agent having an anti-blastomatous and immuno-modulatingeffect, comprising: the medicinal agent including derivatives oftri-p-aminotriphenylchloromethane that can be representedpharmacologically, the medicinal agent having a structural formula:

wherein at least the following applies: R₁═N(CH₃)₂, R₂═H, R₃═H,R₄═N(CH₃)₂, R₅═H, R₆=either NH₂ or NHCH₃ or N(CH₃)₂.
 2. The medicinalagent according to claim 1, wherein the medicinal agent includestri-p-aminotriphenylchloromethane in a form of a tetramethyl derivative,in a structural formula of which R₆═NH₂ and R₁, R₂, R₃, R₄ and R₅correspond to one of named elements and respectively compounds.
 3. Themedicinal agent according to claim 1, wherein the medicinal agentincludes tri-p-aminotriphenylchloromethane in the a form of apentamethyl derivative, in a structural formula of which R₆═NHCH₃ andR₁, R₂, R₃, R₄ and R₅ correspond to one of named elements andrespectively compounds.
 4. The medicinal agent according to claim 1,wherein the medicinal agent includes tri-p-aminotriphenylchloromethanein a the form of a hexamethyl derivative, in a structural formula ofwhich R₆═N(CH₃)₂ and R₁, R₂, R₃, R₄ and R₅ correspond to one of namedelements and respectively compounds.
 5. The medicinal agent according toclaim 3, wherein the medicinal agent includestri-p-aminotriphenylchloromethane in a form of a mixture, thetetramethyl and pentamethyl derivatives of which being at a ratio of2-98 percent by volume tetramethyl derivative and a remainderpentamethyl derivative.
 6. The medicinal agent according to claim 3,wherein the medicinal agent includes tri-p-aminotriphenylchloromethanein a form of a mixture, the tetramethyl and hexamethyl derivatives beingat a ratio of 2-98 percent by volume tetramethyl derivative and aremainder hexamethyl derivative.
 7. The medicinal agent according toclaim 3, wherein the medicinal agent includestri-p-aminotriphenylchloromethane in a form of a mixture, thepentamethyl and hexamethyl derivatives being at a ratio of 2-98 percentby volume pentamethyl derivative and a remainder hexamethyl derivative.8. The medicinal agent according to claim 3, wherein the medicinal agentincludes tri-p-aminotriphenylchloromethane in a form of a mixture, thetetramethyl, pentamethyl and hexamethyl derivatives being at a ratio of2-98 percent by volume tetramethyl derivative, 2-98 percent by volumepentamethyl derivative and a remainder hexamethyl derivative.
 9. Amedicinal agent, which has an anti-blastomatous and immuno-modulatingeffect, comprising: the medicinal agent including a mixture of dextrinand pharmacologically representable derivatives oftri-p-aminotriphenylchloromethane in a form of either tetramethyl,pentamethyl or hexamethyl derivatives or a mixture of tetramethyl andpentamethyl derivatives or respectively a mixture of tetramethyl andhexamethyl derivatives or respectively a mixture of pentamethyl andhexamethyl derivatives or respectively a mixture of tetramethyl,pentamethyl and hexamethyl derivatives at a ratio of 10-95 percent byvolume of the corresponding derivative or respectively a mixture ofderivatives of the tri-p-aminotriphenylchloromethane and a remainderdextrin.
 10. The medicinal agent according to claim 9, wherein a ratioof the mixture of tetramethyl and pentamethyl derivatives is 2-98percent by volume tetra derivative and a remainder pentamethylderivative.
 11. The medicinal agent according to claim 9, wherein aratio of the mixture of tetramethyl and hexamethyl derivatives is 2-98percent by volume tetra derivative and a remainder hexamethylderivative.
 12. The medicinal agent according to claim 9, wherein aratio of the mixture of pentamethyl and hexamethyl derivatives is 2-98percent by volume penta derivative and a remainder hexamethylderivative.
 13. The medicinal agent according to claim 9, wherein aratio of the mixture of tetra methyl, pentamethyl and hexamethylderivatives is 2-98 percent by volume tetra derivative, 2-98 percent byvolume penta derivative and the a remainder hexamethyl derivative. 14.The medicinal agent according to claim 1, wherein the medicinal agentincludes tri-p-aminotriphenylchloromethane in a form of a mixture, thetetramethyl and pentamethyl derivatives being at a ratio of 2-98 percentby volume tetramethyl derivative and a remainder pentamethyl derivative.15. The medicinal agent according to claim 1, wherein the medicinalagent includes tri-p-aminotriphenylchloromethane in a form of a mixture,the tetramethyl and hexamethyl derivatives being at a ratio of 2-98percent by volume tetramethyl derivative and a remainder hexamethylderivative.
 16. The medicinal agent according to claim 1, wherein themedicinal agent includes tri-p-aminotriphenylchloromethane in a form ofa mixture, the pentamethyl and hexamethyl derivatives being at a ratioof 2-98 percent by volume pentamethyl derivative and a remainderhexamethyl derivative.
 17. The medicinal agent according to claim 1,wherein the medicinal agent includes tri-p-aminotriphenylchloromethanein a form of a mixture, the tetramethyl, pentamethyl and hexamethylderivatives being at a ratio of 2-98 percent by volume tetramethylderivative, 2-98 percent by volume pentamethyl derivative and aremainder hexamethyl derivative.